Presently apparatuses are known for monitoring testing or measuring a system in which a fluid that is flowing or substances in the fluid will dissipate in part as it traverses the system or will require regeneration. For example, MRI machines are used today to create images with or without administration of a tracer-contrast agent. Customarily, the machine is controlled to take a series of images at discrete time intervals and the images are then dynamically analyzed to obtain an output result. For example, dynamic studies of contrast enhancement in breast tumors have demonstrated that the rate of change in signal intensity is an important parameter for the distinction of breast masses, leading to pharmacokinetic studies. However, it is known that as a result of tumor heterogeneity, there are significant local variations in the time evolution of contrast enhancement, and, therefore, maintaining high spatial resolution in both the recording and analysis steps is very important. In a standard clinical MRI of the breast, it is difficult to achieve high spatial resolution and also maintain high temporal resolution. In most dynamic studies performed previously, the emphasis was on high temporal resolution (at the expense of spatial resolution) monitoring the equilibration in the intravascular space and early diffusion into the extracellular space of the tissue. As a consequence, in standard MRI machines the output results are sometimes inconclusive.
Prostate cancer is the leading form of cancer diagnosed in males and the second leading cause of cancer-related death in men in the USA, as well as in many other Western countries. One out of every six men is at lifetime risk for prostate cancer. This high prevalence, and a rising age-adjusted mortality rate, makes prostate cancer a major socioeconomic problem. In 2001 alone, an estimated 198,000 men in the United States were diagnosed with prostate cancer and 31,500 succumbed to it.
In the past, prostate cancer was only diagnosed when symptoms of advanced disease appeared. Currently, the best way to detect prostate cancer is to measure the level of the serum prostate specific antigen (PSA) in a blood test and to use a digital rectal examination (DRE) to feel for lumps on the prostate. Additional important tests used to diagnose prostate cancer include: (i) urine test for blood or infection; (ii) transrectal ultrasonography using a probe inserted into the rectum, which creates a picture based on the detection of the echoes of sound waves; (iii) intravenous pilogram of a series of X-ray pictures of the organ and the urinary tract; (iv) cytoscopy inspection of the urethra and the bladder via a thin lighted tube; and (v) biopsy—removing tissue, usually with a hollow needle, for pathologic examination.
Prostate specific antigen (PSA) is an enzyme produced by the epithelial cells of the prostate. Small amounts normally leak into the circulation with reported concentrations of less than 4 ng/ml. However, normal PSA levels may vary with age, for example, from 2.4 ng/ml for men aged 41-50 years to 6.5 ng/ml for men aged 71-80 years. Routine PSA tests are extremely valuable for monitoring for prostate cancer recurrence. A fall in PSA values indicates a favorable response to primary treatment. PSA is not cancer specific, and certain disorders and interventions such as benign prostatic hyperplasia, prostatitis, prostatic infraction, prostate surgery, and a prostate biopsy also elevate the PSA level. The reported sensitivity of the PSA test is 43-81%, and its specificity is 59-93%. Since 25% of men with PSA levels between 4-10 ng/ml have malignant disease, a biopsy is usually recommended for these patients. Of the 15 million men tested in 1998, 15% or 2.25 million men had PSA levels considered higher than normal and thus faced the prospect of biopsy. Because the lesion is difficult to visualize on transrectal ultrasound (TRUS), male prostate biopsies are performed “blindly”, without regard to what may be localized areas. Sampling becomes a key issue in such situations, and over the last years there has been a shift from limited sampling (2 cores on each side), to increase sampling (3 cores on each side or 6 cores on each side and separate sampling of the seminal vesicles). Even with 13 cores, however, it is still possible to completely miss areas of carcinoma, and hence, understage the disease.
The introduction of the FDA-approved PSA serum test in 1987 was followed by a dramatic increase in the findings of new prostate cancers in the USA. Previously, when cancers were largely being diagnosed based on symptoms alone, the detection rate with DRE was only 1%, and 30% of patients had a clinically localized, potentially curable disease. In the PSA screening tests of men without symptoms, detection rates are as high as 5%, and 70%-98% of the patients have a potentially curable disease. The improvement in biopsy techniques with respect to technology and method of sampling the prostate has resulted in an improved early detection of smaller tumors.
Staging and grading of prostate cancer are vital for the management of the disease. Staging is a careful attempt to find out whether the cancer has spread and, if so, what parts of the body are affected. The results of staging are useful for selecting the appropriate therapy for the patient. The stages are characterized as follows. In stage I, the cancer cannot be detected by a rectal examination and causes no symptoms. Stage I tumors may be in more than one area of the prostate, but with no evidence of spread outside the prostate. In stage II, the tumor is felt by DRE or detected by the PSA test, but there is no evidence of spread outside the prostate. In stage III, the cancer has spread to nearby tissues, and in stage IV, to the lymph nodes or to other parts of the body.
Grading determines the pathologic nature of the cancer with reference to normal prostate tissue, primarily in relation to the state of aggressiveness and growth capacity of the cancer. The Gleason system is the predominant system used in describing prostate carcinoma grade. It is based on the assessment of two properties: differentiation and likelihood for the prostate cancer to spread, i.e., the tumor metastatic capacity.
Prediction of disease stage from preoperative information is possible, especially in the extremes. Several models were developed based on preoperative features such as: (i) PSA serum level (a PSA value between 4 and 10 ng/ml detects organ confined disease in 75% of cases, but this proportion decreases to 48% if the PSA value is greater than 10 ng/ml; a PSA value greater than 40 ng/ml is generally indicative of metastatic disease); (ii) the prostate gland volume as measured by ultrasound; (iii) the tumor volume as measured by DRE; (iv) the tumor length and volume on core biopsy; (v) biopsy sampling methods; (vi) PSA density; (vii) microvessel density; and (viii) histologic grade, as measured by the Gleason method.
The three most used method for the diagnosis of prostate cancer are computed tomography (CT), TRUS and MRI. All these methods have been evaluated as tools for staging prostate cancer. Of the three, MRI appears to have the greatest potential utility in providing diagnostic information, i.e. detection, staging and biopsy guidance. CT has reported accuracies ranging from 47%-75% for local staging of prostate cancer. Even though at the higher accuracies CT could compete with TRUS, it is generally not used for local staging of prostate cancer. Even though the accuracy of TRUS in staging prostate disease has been reported to be as high as 86% and as low as 38%, most reports indicate the TRUS is not as valuable as MRI in local staging. The major role of TRUS is in guiding needle biopsies. In addition, TRUS has been the modality of choice in determining prostatic volumes, even though there is some reader variability reported for these volume measurements.
The soft tissue contrast of MRI and the ability of MRI to acquire multi-planar images have increased its ability to evaluate the internal pelvic structures. T1-weighted images maximize the contrast between fat and solid organs or viscera and have been used to evaluate lymphadenopathy. T2-weighted images characterize the internal structure of solid organs and provide a high contrast between tumor and normal muscular tissue. However, this distinction is often lost in the prostate and depends on the location of the pathologic changes within the prostate. Due to similarities between tumor and central gland tissues, poor discrimination results, particularly in the presence of coexisting benign disease. No significant improvement in the detection of extra-capsular extension was reported when fat-suppressed T2-weighted images were applied.
Pelvic MRI based on relaxation weighted imaging did not show a marked improvement in prostate cancer staging. As a result of this low accuracy, investigators have turned to use endorectal MRI coils in order to increase the sensitivity and specificity of MR imaging. The staging accuracy for endorectal coil MRI in preliminary studies varied between 68% and 82%. Staging of local disease was considerably poorer at 57%. The utility of endorectal imaging for prostate cancer has not been universally accepted. Yet, multivariable analysis has shown that endorectal MRI findings of extracapsular extension is the single most significant predictor of pathology at radical prostatectomy when compared with clinical staging, serum PSA level, or the Gleason score on biopsy. Most researchers believe that endorectal imaging may be especially useful for the determination of seminal vesicle involvement, though extra-capsular extension can often be detected as well.
The use of contrast-enhanced MRI to diagnose prostate diseases has so far been limited. Recently, the ability of dynamic contrast-enhanced MRI to differentiate benign from malignant prostatic disease has been evaluated (Liney G P, Turnbull L W and Knowles, 1999, In vivo magnetic resonance spectroscopy and dynamic contrast enhanced imaging of the prostate gland, NMR in Biomedicine, 12, pp. 39-44; Turnbull L W et al., 1999, JMRI 9, pp. 311-316). The first study included 20 patients, and the second 13 patients who were candidates for radical prostatectomy based on transrectal ultrasound findings and negative radioisotope bone scans. Maps at pixel resolution of the maximum enhancement factor value and of the time taken to reach maximum enhancement were calculated. Significant contrast-uptake was observed with faster enhancement in tumor regions than in benign prostatic hypertrophy (BPH) regions. Considerable discrimination between the different regions was obtained, emphasizing the potential of contrast enhanced MRI in staging prostate cancer patients. In both studies, high temporal resolution (11 sec.) and low spatial resolution (6-7 mm slice thickness) were applied. It was indicated that the low spatial resolution in these studies is a serious limiting factor, especially when dealing with heterogeneous lesions.
Accepted standard treatments for prostate cancer include careful observation, surgery (radical prostatectomy, transurethral resection of the prostate), radiotherapy and hormone therapy. Many men, mostly elderly, whose prostate cancer is progressing slowly and is detected at an early stage, may not need treatment and undergo careful observation. For these patients, the possible risk and side-effects of surgery and treatment may outweigh the possible benefits of treatment. The decision as to who will benefit from a prostatectomy is a major issue. Clearly, some of these men die before their prostate carcinoma causes significant problems and such tumors have been described as “insignificant.” Others undergo a radical prostatectomy only to discover that their tumors have grown beyond the prostate, and 50% of these men will suffer a recurrence. Finally, there are patients who will most likely benefit from radical prostatectomy.
The staging and prognosis of patients at the lower and upper ends of the Gleason score spectrum are more readily predicted. However, most patients today are found initially with these parameters in an intermediate range. Additional information about disease extent is needed for early and accurate staging and treatment, as well as to determine a better means to follow patient progress.
Currently, however, there is no precise clinical method for the reliable assessment of local extent of prostate cancer. This is a major drawback in the treatment of localized disease.